An osteogenesis accelerator is one of drugs which have been desired with the progression of the aging society in recent years, and as the accelerator, BMP (bone morphogenetic protein) or the like has been clinically used at present. However, the treatment with BMP has a problem that a satisfactory effect can not be obtained since any self regulatory mechanism acts on an osteogenetic activity of BMP. Although the cause of this has not been elucidated, the rapid disappearance of BMP from a grafted site, a negative feedback mechanism and the presence of an endogenous inhibitory substance have been considered as the cause [e.g., see Takase M et al., “Biochem Biophys Res Commun.” published by Elsevier Science (U.S.A.), 1998, vol. 244, p. 26-29 and Valentin-Opran A et al., “Clin Orthop.” published by Lippincott Williams & Wilkins (U.S.A.), 2002, vol. 395, p. 110-120].
BMP was discovered as a factor inducing heterotopic osteogenesis by Urist in 1965 [e.g., see Urist M R, “Science” published by American Association for the Advancement of Science (U.S.A.), 1965, vol. 150, p. 893]. Thereafter, DNA loning of human BMP succeeded [e.g., see Wozney J M et al., “Science” published by American Association for the Advancement of Science (U.S.A.), 1988, vol. 242, p. 1528-1534], which made it possible to produce recombinant human BMP (rhBMP). Accordingly, BMP has been clinically applied in the expectation that the bone defect would be efficiently repaired for a shorter period of time. BMP is one of molecules belonging to the TGF-β superfamily, and it has been known to accelerate chondrogenesis, fat formation and osteogenesis and to inhibit muscle formation from mesenchymal stem cells [e.g., see Katagiri T et al., “J. Cell Biol.” published by Rockefeller University Press (U.S.A.), 1994, vol. 127, p. 1755-1766; Ahrens Metal., “DNA Cell Biol.” published by Mary Ann Liebert inc. publishers (U.S.A.), 1993, vol. 12, p. 871-880 and Asahina I et al., “Exp. Cell Res.” published by Elsevier Science (U.S.A.), 1996, vol. 222, p. 38-47].
TGF-β has been known to have an activity of controlling growth and differentiation of various cells including fibroblasts which are main cells constituting fibrous tissues and an activity of controlling the production and deposition of extracellular matrices indispensable for wound healing. Meanwhile, an activity of TGF-β on bones is unclear in many points, and there are reports stating that TGF-β acts positively on osteogenesis [e.g., see Erlebacher A et al., “J. Cell. Biol.” published by Rockefeller University Press (U.S.A.), 1996, vol. 132, p. 195-210 and Alliston T et al., “EMBO J.” published by Oxford University Press (England), 2001, vol. 20, p. 2254-2272] and reports stating that TGF-β acts negatively thereon [e.g., see Noda M et al., “Endocrinology” published by Endocrine Society (U.S.A.), 1989, vol. 124, p. 2991-2994 and Joyce M E et al., “J. Cell Biol.” published by Rockefeller University Press (U.S.A.), 1990, vol. 110, p. 2195-2207].